Testosterone increases and estradiol decreases middle cerebral artery occlusion lesion size in male rats

This study was undertaken to determine the effects of estrogen and testosterone on cerebral ischemic lesion size induced by middle cerebral artery (MCA) occlusion in male rats. Rats were gonadectomized and treated with testosterone, estrogen, or testosterone plus estrogen filled Silastic® pellets. The animals were divided into 6 groups: intact, intact+estrogen (E2), castrate, castrate+testosterone (T), castrate+E2, and castrate+T+E2. One week after treatment, cerebral ischemia was induced by MCA occlusion for 40 min, followed by reperfusion. After 24 h, rats were sacrificed and slices were then stained to assess lesion size. The presence of testosterone increased and the removal of testosterone decreased lesion size. A strong positive correlation (r²=0.922) between plasma testosterone concentrations and ischemic lesion size was observed. Estradiol treatment reduced ischemic area. In summary, the present study provides evidence that testosterone exacerbates and estrogens ameliorate ischemic brain damage in an animal model of cerebral ischemia.     

Effects of treadmill training on motor performance and extracellular glutamate level in striatum in rats with or without transient middle cerebral artery occlusion

Glutamate transmission is essential for learning and memory. Several studies have shown that exercise can up-regulate the expression of brain-derived neurotrophic factor (BDNF) in normal brain, thus enhancing glutamate release through the synaptic-associated protein synapsin I in vitro. The aim of this study was to investigate the effects of treadmill training on the release of these factors in the striatum and on the motor function in both normal and brain-ischemic rats. Rats were randomly assigned to normal and brain-ischemic groups. Those in the brain-ischemic group underwent middle cerebral artery occlusion (MCAO) for 1 h. Fifty percent of the rats in each group underwent treadmill training for 14 days. The rest remained relatively inactive for 14 days and served as the control groups. Motor function was assessed by performing three motor tests (foot-fault-placing, parallel-bar-crossing, and ladder-climbing tests). Our data showed that after treadmill training, motor function improved significantly in both normal and brain-ischemic rats when compared with the corresponding controls. The levels of glutamate, BDNF, and p-synapsin I were also up-regulated by treadmill training. These results suggested that the overall responses to treadmill training were similar in both normal and brain-ischemic rats. The beneficial effects of treadmill training might be partly due to the involvement of glutamate in neuronal activity in both brain-ischemic and normal rats.     

Comparison of three different time points of starting treadmill training in spinal cord injured rats

Objective: It has been widely acknowledged that early treadmill training plays an important role in rewiring neurons in a functionally meaningful manner in spinal cord injury (SCI) treatment. However, it is still unclear how early to start treadmill training to obtain the most efficacious results after SCI. The purpose of this study was to find the earliest time point when treadmill training was most effective in rewiring neurons.

Methods: The rats were randomly divided into five groups: a sham group, control group, and three treadmill groups based on training start time post-injury: a 24?h group, 48?h group, and 72?h group.

Results: The results revealed that in the 72?h group, Basso, Beattie, and Bresnaham scores increased and apoptotic cells decreased significantly compared to the other groups. There were no statistically differences in neuron counting and 5-bromo-2V-deoxyuridine assays between the groups.

Conclusion: These results indicated that the best start time for treadmill training is 72?h after SCI.     

The effects of treadmill walking combined with obstacle-crossing on walking ability in ambulatory patients after stroke: a pilot randomized controlled trial

Background and objective: Treadmill walking training (TWT) provides greater amount and intensity of stepping practice than conventional walking training in patients with chronic stroke. However, there is not any conclusive evidence regarding the effects of TWT for ambulatory post-stroke patients. This study investigated the effects of treadmill walking combined with obstacle-crossing on the walking ability of ambulatory post-stroke patients.

Methods: Twenty-nine subjects from a university hospital-based rehabilitation center were randomly assigned to one of the following: experimental group (15 subjects) or control group (14 subjects). All subjects underwent 30 min of active/passive exercises and 30 min of gait training in the form of treadmill walking. The subjects in the experimental group underwent simultaneous training in obstacle-crossing while walking on the treadmill for 30 min/day, 5 times/week, for 4 weeks. Main measures were the 10-m walk test (10MWT), 6-min walk test (6MWT), Berg Balance Scale (BBS), timed “Up & Go” (TUG) test, and Activities-specific Balance Confidence (ABC) scale used before and after the intervention.

Results: The changed values of the 6MWT and BBS were significantly higher in the experimental group than in the control group after adjusting for each baseline value, with large effects of 1.12 and 0.78, respectively, but not in the 10MWT, TUG, and ABC scale scores. Both groups showed a significant difference in all variables before and after the intervention.

Conclusion: Treadmill walking combined with obstacle-crossing training may help improve the walking ability of patients with hemiplegic stroke and can possibly be used as an adjunct to routine rehabilitation therapy as a task-oriented practice based on community ambulation.     

桃仁红花煎剂对大鼠缺血再灌注后脑组织的保护作用

目的研究桃仁红花煎剂对大鼠局灶性脑缺血再灌注后脑组织的影响。方法 45只雄性SD大鼠随机平均为给药组、模型组和对照组。采用线栓法阻塞大鼠右侧大脑中动脉,使其缺血2h后再灌注24h建立局灶性脑缺血再灌注模型。术前2h和术后3、12h分3次灌胃给予桃仁红花煎剂,总剂量是40g/kg。通过神经行为评分评定大鼠神经功能变化,按干湿重法测定脑含水量,用氯化三苯基四氮唑法测定脑梗死范围,分光光度法测定缺血区脑组织中Na+-K+-ATP酶和Ca2+-ATP酶的活性。结果在缺血再灌注3h和24h后,给药组神经行为评分明显高于模型组(P<0.05)。缺血再灌注24h,给药组脑含水量和脑梗死体积明显少于模型组(P<0.05);给药组缺血脑皮层中Na+-K+-ATP酶和Ca2+-ATP酶活性明显高于模型组(P<0.05)。结论桃仁红花煎剂对大鼠缺血再灌注后脑组织有保护作用,其机制可能与其增强Na+-K+-ATP酶和Ca2+-ATP酶的活性、减轻脑水肿有关。     

急性鼠脑缺血时选择性酶抑制剂的脑保护作用

目的 研究７－硝基吲唑（７－ＮＩ）在大鼠脑缺血后的保护作用。方法 用线栓法建立大鼠大脑中动脉缺血模型。用７－ＮＩ（选择性ｎＮＯＳ抑制剂）研究了鼠脑缺血过程中脑组织ＮＯＳ活性梗死体积以及梗死外周区神经元变化。结果 ７－ＮＩ明显抑制了神经元型ＮＯＳ活性,减少了脑梗死体积并显著减轻了神经元缺血早期变性变化。结论 ７－ＮＩ对因急性期脑组织有明显保护使用。     

Effects of task-oriented treadmill-walking training on walking ability of stoke patients

Background: Generally, treadmill-walking training focuses on weight bearing and the speed of walking. However, changes in direction, speed, and slope while walking require adaptation.

Objective: The effects of task-oriented treadmill-walking training (TOTWT) on the walking ability of stroke patients were evaluated.

Methods: Subjects were randomly divided into two groups: the task-oriented treadmill-walking training (TOTWT) group and the conventional treadmill-walking training (CTWT) group. Evaluation was performed before the commencement of the training and again 4 and 8 wk after training was initiated. The OptoGait system measured gait parameters. The Timed Up and Go test and 6-min walk test were also performed.

Results: Within each group, both the TOTWT and the CTWT groups significantly differed before and after the intervention in all tests (P < 0.05); the CTWT group showed greater improvement in all tests following TOTWT (P < 0.05).

Conclusion: TOTWT improves gait and rehabilitation in the stroke-affected limb, and also improves general gait characteristics.     

Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats

Stroke is a leading cause of long-term disability worldwide; survivors often show sensorimotor and cognitive deficits. Therapeutic exercise is the most common treatment strategy for rehabilitating patients with stroke via augmentation of neurogenesis, angiogenesis, neurotrophic factors expression, and synaptogenesis. Neurogenesis plays important roles in sensorimotor and cognitive functional recovery, and can be promoted by exercise; however, the mechanism underlying this phenomenon remains unclear. In this study, we explored the effects of treadmill exercise on sensorimotor and cognitive functional recovery, as well as the potential molecular mechanisms underlying the promotion of neurogenesis in a rat model of transient middle cerebral artery occlusion (tMCAO). We found that treadmill exercise facilitated sensorimotor and cognitive functional recovery after tMCAO, and that neural stem/progenitor cell proliferation, differentiation, and migration were enhanced in the ipsilateral subventricular and subgranular zones after tMCAO. Meanwhile, the newborn neurons induced by treadmill exercise after tMCAO had the similar function with pre-existing neurons. Treadmill exercise significantly increased CD200 and CD200 receptor (CD200R) levels in the ipsilateral hippocampus and cortex. Further study revealed that treadmill exercise-induced neurogenesis and functional recovery were clearly inhibited, while Il-β and Tnf-α expression were upregulated, following lentivirus (LV)-induced suppression of post-stroke CD200R expression. Consistent with the effect of treadmill exercise, CD200Fc (a CD200R agonist) markedly promoted neurogenesis and functional recovery after stroke. In addition, CD200Fc could further enhance the functional recovery induced by treadmill exercise after stroke. Our results demonstrate the beneficial role of treadmill exercise in promoting neurogenesis and functional recovery via activating the CD200/CD200R signaling pathway and improving the inflammatory environment after stroke. Thus, the CD200/CD200R signaling pathway is a potential therapeutic target for functional recovery after stroke.     

促红细胞生成素对大鼠脑损伤后神经保护作用的实验研究

目的探讨促红细胞生成素(EPO)对颅脑损伤后的神经保护作用。方法成年SD大鼠55只,随机分为假手术组(n=5)、对照组(n=25)和EPO治疗组(n=25);对照组和治疗组采用改进的Feeney等人的方法制作脑创伤模型,根据伤后处理时间点每组再分为5个亚组,即伤后6h、24h、48h、72h和168h组,每亚组5只动物。检测各组动物在EPO处理前后不同时间点神经行为评分和脑含水量变化;放射免疫法检测肿瘤坏死因子(TNF-α)与白介素-1β(IL-1β)的水平。结果与对照组相比,在脑损伤后24～48hEPO治疗组神经行为评分明显增加(P0.05),在伤后48～168h脑含水量明显降低(P0.05)。在颅脑损伤后6～168hEPO治疗组血清TNF-α含量明显低于对照组(P0.05),而血清IL-1β的含量在伤后24～168hEPO治疗组也明显低于对照组(P0.05)。结论本研究提示EPO对大鼠脑损伤后的神经有保护作用。     

喹硫平对脂多糖损伤后海马神经干细胞的保护作用

目的：探讨喹硫平（QUE）对脂多糖（LPS）损伤后海马神经干细胞（NSCs）活性的作用及增殖情况的影响,并初步研究胞外信号调节激酶（ERK ）信号通路在其中的作用。方法建立体外大鼠海马NSCs的LPS损伤细胞模型,分为对照组（Sham组）、LPS组、LPS＋ QUE组（包括0．5μmol／L、1μmol／L和2μmol／L三个不同剂量组）,作用48 h后,采用WST －8试剂检测细胞活性,蛋白质印迹（Western Blot）法检测磷酸化胞外信号调节激酶1／2（pERK1／2）的表达水平,5－溴脱氧尿嘧啶核苷（BrdU ）检测细胞增殖情况。并在培养基中添加ERK磷酸化抑制剂U0126,以进一步明确ERK信号通路在其中的作用。结果（1）细胞活力：与Sham组[吸光度值（0．371±0．027）]相比,LPS组（0．251±0．034）细胞活力显著下降（P ＜0．01）,而 LPS＋ QUE 1μmol／L 组（0．311±0．018）和 LPS＋ QUE 2μmol／L组（0．343±0．021）均显著抑制了LPS对其活力的影响（与LPS组相比,P＜0．05）。（2）West‐ern Blot结果显示,LPS组的pERK1／2表达水平（0．313±0．124）明显低于Sham组（1．417±0．141）及LPS＋QUE 1μmol／L组（0．681±0．098）组和LPS＋QUE 2μmol／L组（0．954±0．119）（P＜0．05）,而LPS组与LPS＋QUE 0．5μmol／L组（0．368±0．123）的pERK1／2表达水平接近。（3）BrdU 染色结果显示,LPS组的BrdU阳性细胞数百分比（23．098±2．153）％明显低于Sham组（40．388±2．910）％, LPS＋QUE 1μmol／L 组（28．742±1．536）％和 LPS＋ QUE 2μmol／L 组（31．369±2．313）％（P ＜0.05）。（4）U0126可抑制QUE（1μmol／L和2μmol／L）的上述作用。结论 QUE能抑制LPS导致的NSCs损伤,这种作用与调节ERK1／2的磷酸化有关。